This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Metastasis and subsequent resistance to tamoxifen therapy is a major cause of death in patients with breast cancer. Approximately 50% of patients with recurrent disease appear non-responsive to tamoxifen, resulting in progressive disease, while the other half shows objective response. Therapy-resistance is not fully understood and available predictors work only in ~50% of the cases. Clearly, new markers are needed to better predict therapy efficacy, and develop targets for new therapies. The ultimate goal of this study is to identify proteins that associate with therapy-resistance using high-resolution liquid chromatography coupled with high performance mass spectrometry (nanoLC-FTMS) and validate candidate biomarkers using targeted LC-MS approaches and immunohistochemistry.